Exclusive Photothermal Heat Generation by a Gadolinium Bis(naphthalocyanine) Complex and Inclusion into Modified High-Density Lipoprotein Nanocarriers for Therapeutic Applications

Exclusive Photothermal Heat Generation by a Gadolinium Bis(naphthalocyanine) Complex and Inclusion into Modified High-Density Lipoprotein Nanocarriers for Therapeutic Applications
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DOI:
10.1021/nn403384k
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发表时间:
2013-10-01
期刊:
影响因子:
17.1
通讯作者:
Imahori, Hiroshi
Imahori, Hiroshi
中科院分区:
材料科学1区
文献类型:
--
作者:
Mathew, Simon;Murakami, Tatsuya;Imahori, Hiroshi

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一种疏水钆双(萘菁)夹心复合物(GdSand)在可见光和红外波长(高达2500 nm)具有多种吸光度,通过摄取到新生突变型高密度脂蛋白(HDL)纳米载体中,在水溶液中溶解。高密度脂蛋白纳米载体还被转录肽序列的反式激活子功能化,以促进药物传递系统(cpHDL)的有效细胞渗透。染料负载纳米载体(GdSand@cpHDL)在近红外(NIR)激光照射下表现出光热产热特性,其产热能力随入射激光功率的变化而变化。在cpHDL纳米载体(即ICG@cpHDL)中,比较了染料GdSand和已开发的分子光热剂吲哚菁绿(ICG)的光热行为,发现GdSand@cpHDL具有两个显著优势:(1)在长时间的光吸收下保持高温的能力,同时降低了染料的自毁程度;(2)完全光热产生,没有可检测到的单线态氧产生,从而提高了辐照后cpHDL纳米载体的完整性。最后,GdSand@cpHDL成功地进行了一项针对NCI-H460人肺癌细胞的体外研究,证明了镧系夹层复合物在光热治疗应用中的原理验证。
A hydrophobic gadolinium bis(naphthalocyanine) sandwich complex (GdSand) possessing several absorbances across visible and infrared wavelengths (up to 2500 nm) was solubilized in aqueous solution by uptake into a nascent mutant high-density lipoprotein (HDL) nanocarrier. The HDL nanocarrier was additionally functionalized with a trans-activator of transcription peptide sequence to promote efficient cell penetration of the drug delivery system (cpHDL). The dye-loaded nanocarrier (GdSand@cpHDL) exhibited photothermal heat generation properties upon irradiation with near-infrared (NIR) laser light, with controllable heat generation abilities as a function of the incident laser light power. Comparison of the photothermal behavior of the dyes GdSand and the well-explored molecular photothermal agent indocyanine green (ICG) in the cpHDL nanocarrier (i.e., ICG@cpHDL) revealed two significant advantages of GdSand@cpHDL: (1) the ability to maintain elevated temperatures upon light absorption for extended periods of time, with a reduced degree of self-destruction of the dye, and (2) exclusive photothermal heat generation with no detectable singlet oxygen production leading to improved integrity of the cpHDL nanocarrier after irradiation. Finally, GdSand@cpHDL was successfully subjected to an in vitro study against NCI-H460 human lung cancer cells, demonstrating the proof-of-principle utility of lanthanide sandwich complexes in photothermal therapeutic applications.